The Role of Iron Status in Pediatric Asthma Severity

Research Article

J Blood Disord. 2020; 7(1): 1059.

The Role of Iron Status in Pediatric Asthma Severity

Ali HA1*, Deraz TE1, Ibrahim NR2, Mohamed YH3 and Ahmed AH1

1Department of Pediatrics, University of Ain Shams, Egypt; Email: tharwat_deraz

2General Practitioner, Ministry of Public Health, Egypt; Email: [email protected]

3Department of Pediatrics, Misr University, Egypt; Email: [email protected]

*Corresponding author: Ali HA, Department of Pediatrics, University of Ain Shams, Egypt

Received: June 19, 2020; Accepted: July 24, 2020; Published: July 31, 2020


Higher iron status has been associated with a lower prevalence of asthma and asthma attacks. However, the associations between iron status and asthma-related outcomes have not been well investigated in pediatrics. For this reason, we evaluated the iron status in asthmatic children and determined its relation to clinical asthma severity. A total of seventy cases aged from 6-17 years were recruited in this study - including fifty asthmatic patients and twenty age and sex-matched healthy controls. Complete blood count, iron profile including (Serum iron, ferritin, Total Iron Binding Capacity (TIBC) and transferring saturation) were measured in patients and controls and according to them, asthmatic patients were divided into asthmatic children without Iron Deficiency Anemia (IDA), asthmatic children with IDA. Associations between iron status and the severity of bronchial asthma were assessed in the patient groups. The study found that IDA was presented among 34% of the studied asthmatic patients compared to 20% in the control group (P<0.001). Moreover, the asthmatic attacks were significantly more frequent and severe in asthmatics with IDA (88.3%, 64.7%) than those without IDA (51.5%, 45.5%) (P<0.001) with frequent emergency room visits and hospital admissions among asthmatics with IDA (70.6%, 41.1%) (P=0.037, 0.041). Thus IDA is prevalent among asthmatic children and lower iron status has been associated with higher rates of asthma attacks and more severe course of the disease.

Keywords: Asthma; Asthma Attacks; Iron Deficiency Anemia; Pediatric; Severity.


CBC: Complete Blood Count; TIBC: Total Iron Binding Capacity; IDA: Iron Deficiency Anemia; ER: Emergency Room; ICU: Intensive Care Unit; BMI: Body Mass Index; Hb: Hemoglobin; GINA: Global Initative for Asthma; K3EDTA: Tripotassium Ethylene Diamine Tetraacetic Acid; Hct: Hematocrit; MCV: Mean Corpuscular Volume, MCH: Mean Corpuscular Hemoglobin; RDW: Red Cell Diameter Width; ELISA: Enzyme-Linked Immunosorbent Assay; RBCs: Red Blood Cells; URTIs: Upper Respiratory Tract Infections


Asthma is common public health problem worldwide [1] and it is a major cause of morbidity and mortality among the pediatric age group [2]. Asthma is defined as a chronic disorder of the airways that's complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyper responsiveness, and an underlying inflammation.The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment [3].

Iron Deficiency Anemia (IDA) is that the commonest nutritional disorder within the world. The prevalence of anemia was found to be especially high among children especially in the developing countries [4,5]. IDA is a common disease in Egypt, with a very high prevalence. Egypt Demographic Health Survey reported a 48.5% prevalence of iron deficiency anemia among Egyptian children and 26.6% among Egyptian adults [6].

Childhood asthma is associated with increased rates of doctor visits, hospitalizations, school absenteeism, parental work absenteeism, child activity limitations, and child disability [7,8]. Furthermore, iron deficiency is also associated with impaired immune competence, and therefore, can lead to increased morbidity [9].

Iron deficiency exerts adverse effects on immune response [10]. Disruptions in iron homeostasis with decreased concentrations of available metal can initiate pathophysiologic events culminating in asthma. Such events include (1) inflammation and (2) muscle contraction involved in bronchoconstriction and obstruction [11].

Imbalance between Oxidative Stress (OS) and antioxidant system is present in IDA patients. Oxidative damage to cells can be caused by the formation of superoxide radicals that affect the equilibrium between prooxidants and antioxidants in biological systems which play an important role in the pathophysiology of asthma [12-14].

Material and Method

Study Design and Setting

This cross sectional case control study was conducted on a total of seventy children aged from 6-17 years during the period from May 2017 to May 2018 -Fifty asthmatic children who attended pediatric chest clinic, Children’s Hospital, Ain Shams University, Egypt, and twenty healthy children with matched age and sex as the study group who attended the out-patient clinic for non respiratory problems and without any history suggestive of asthma, allergy, or family history of atopic diseases,were taken as controls.

Study Subjects

The patients were included in the study if they have documented asthma diagnosis. Asthmatic children were diagnosed by clinical examination together with applying the following criteria [15-17]:

  1. Episodic symptoms of airflow obstruction.
  2. The demonstration of variable expiratory airflow limitation by spirometry “post-bronchodilator changes in FEV1>12 %” [18].
  3. A history of more than three episodes.
  4. An alternative diagnosis was excluded.

The patients were excluded from the study if 1) they had anemia other than IDA, 2) they were taking any iron supplementation at the time of the study or in the previous three months prior to the study, 3) they had chronic lung diseases other than asthma as bronchiectasis or cystic fibrosis or if 4) They have any systemic illness as congenital heart disease, protein energy malnutrition or immunodeficiency.

Study Methods

A detailed history was taken from the study participants including personal data as age, gender, consanguinity, presenting symptoms as cough, dyspnea, wheezes, respiratory distress, pallor with a special stress on frequency of asthma attacks Emergency Room (ER) visits, hospital and Intensive Care Unit (ICU) admissions. A thorough clinical examination was conducted including full general examination, anthropometric measurements including (the weight, length or height and Body Mass Index (BMI) were measured using standardized methods, the calculation of BMI was done by dividing the weight in kilograms on height meters squared). Full chest examination and laboratory investigations including CBC and iron profile (Serum iron, serum iron binding capacity, serum ferritin and transferrin saturation) were done for the studied patients and controls.

A child was considered anemic if the Hemoglobin (Hb) level was below 11 g/dL [19]. The diagnosis of iron deficiency anemia was supported by criteria provided by World Health Organization guidelines [20,21].

Asthma exacerbation was identified by the following clinical signs (the use of accessory muscles of respiration, chest wall retractions, tachypnea, the presence of inspiratory and expiratory wheezing and cyanosis) [22].

Asthma exacerbations were classified as mild, moderate, severe, or life threatening according to GINA guidelines 2017 and National Asthma Education and Prevention Program guidelines [15,23]. Criteria for severity were based on symptoms and physical examination parameters, as well as lung function and oxygen saturation [24].

Study Procedure

Blood sampling was performed by withdrawal of 5 ml of venous blood by veni-puncture under complete aseptic conditions using K3EDTA tube, non additive chemical tube for the CBC and the iron profile, respectively.

Complete Blood Count (CBC) with peripheral smear was done using Beckman Couller-Gen system and it included the levels of (Hemoglobin (Hb), Hematocrit (Hct), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH) & Red Cell Diameter Width (RDW), Platelets count, Reticulocyte count) and was compared to age related reference range [25].

Iron studies including (Serum ferritin level by ELIZA, Total Iron Binding Capacity values (TIBC) and Serum iron by spectrophotometer, Transferrin saturation was calculated by using the following formula: iron level/TIBC×100) were compared to age related reference range [26].

The study was approved by the Ethics Research Committee of the faculty of medicine, Ain Shams University. All patients were invited to participate and informed consents were obtained from the parents and children older than 8 years prior to inclusion in the study.

Statistical Analysis

The results were statistically analyzed using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA) [27]. Quantitative data were expressed as mean± Standard Deviation (SD). Qualitative data were expressed as frequency and percentage. Correlation between various variables was done using Pearson correlation equation for measuring linear relation in normally distributed variables and P value less than 0.05 was considered to be statistically significant.


The study included seventy children -Fifty cases diagnosed as bronchial asthma, twenty healthy children taken as controls aged from 6 to 17 years. The studied subjects were divided according to CBC and iron profile into group A (asthmatic children without IDA) (n=33), group B (asthmatic children with IDA) (n=17), and group C as controls, (n=20). The IDA was presented in 34% of all asthmatics versus 20% in the controls (P=<0.001).

There was no statistically significant difference between groups A, B and C regarding demographic data and anthropometric measurements, P value>0.05.

Table 1 summarizes the CBC parameters among the three studied groups where in asthmatics with IDA, mean HCT%, HB, MCV, MCH (33.38±1.23, 11.18±0.47, 69.22±3.44, 23.07±1.87) were significantly lower than asthmatics without IDA (37.9%1±1.39, 12.78±±2.66, 25.44±1.29,) and controls (37.19±2.95,12.66±0.85,76.25±4.13, 26.22±1.93), (p< 0.001, p < 0.001, p < 0.001, p < 0.004). While, mean platelets count and RDW were significantly higher in asthmatics with IDA (360.12±85.08, 15.34±1.19) than asthmatics without IDA (344.79±50.57, 13.99±0.74) and controls (338.15±85.67, 11.95±0.74) respectively (P=0.018, 0.004).

The iron profile among the studied groups was presented in Table 2, The mean serum iron, ferritin and transferrin saturation were significantly lower in Group B (74.20±42.13, 11.65±8.87, 27.63±10.92) than Group A (140.21±34.02, 31.24±14.76, 59.01±28.90) and C (106.18±31.55, 17.30±20.41, 31.04±24.12), while mean TIBC was significantly higher in group B (430.06±109.37) than Group A (326.00±107.61) and C (288.70±77.98), P value = .0.029, 0.014, 0.008, 0.037 respectively.

Also, there was a statistically significant difference between group A and group B according to asthma grading as shown in (Table 3) in which moderate to severe persistent asthma was more prevalent in group B (35.2%) than Group A (9.1%), denoting a more severe airway disease in asthmatics with IDA P=0.032.

 As shown in Table 4, Table 5; frequent and severe asthmatic attacks were more pronounced among the anaemic group where the asthmatic attacks were significantly more frequent in group B (88.3%) than in group A (51.5%), with higher moderate to severe exacerbations in group B (64.7%) than group A (45.5%) (P value =0.0548, 0.0437). Also, as regard seeking medical care, frequent ER visits and hospital admissions (in the last year) were significantly higher in group B (70.6%), (41.1%) than group A (60.6%), (3.0%) respectively. (P value=0.037, 0.041). Also the number of ICU admissions (in the last year) was higher in group B (47%), than group A (42.5%), although it was statistically non-significant, which indicates a more severe disease in asthmatics with IDA than asthmatics without IDA (P value= 0.446).

Finally, there was a statistically significant negative correlation between duration of asthma with serum ferritin level (P= 0.007) in which a longer duration of asthma was associated with a lower ferritin levels and vise versa as shown in Figure 1.